1. The Field of the Invention
This invention relates to implantable peritoneal injection catheters and, more particularly, to novel apparatus and methods for minimizing obstruction of subcutaneous peritoneal injection catheters during the period of implantation.
2. The Prior Art
A large proportion of the various chemical reactions that occur in the body are concerned with making energy in foods available to the various physiological systems in the cells. Metabolism of glucose is particularly important in many of these chemical reactions, and the body has a very sophisticated regulatory system adapted to maintain blood glucose levels at an optimum level so that adequate amounts of glucose will be available as needed.
One of the most important elements in the glucose regulatory system is the hormone "insulin." Insulin is a relatively small protein, having a molecular weight of only 5743 daltons; it is comprised of two amino acid chains connected by a pair of disulfide linkages.
Insulin has the ability to regulate glucose metabolism in two ways. First, insulin has the ability to increase the rate of glucose transport through the cell membrane of many types of cells in the body. In the absence of insulin, the rate of glucose transport into these cells is reduced to less than one-fourth of the normal rate. On the other hand, excessive levels of insulin can increase the rate of glucose transport to nearly five times normal. Adjustments in the level of insulin in the body can thus be seen to have the capability of adjusting the rate of glucose absorption by twentyfold.
In addition to its role in glucose transport, insulin also acts as a regulatory hormone. Normally, when digestion results in rising levels of glucose in the body, certain cells in the pancreas, known as "beta cells" of the "islets of Langerhans," commence secreting insulin into the portal vein. About half of the secreted insulin is immediately absorbed by the liver, with the remaining portion being distributed through most of the rest of the body.
In response to the rising level of insulin, the liver produces large quantities of an enzyme known as glucokinase which causes conversion of glucose into glycogen which is then stored. Importantly, a large portion of the excess glucose entering the blood system as a product of digestion is rapidly removed by the liver in order to maintain relatively normal concentrations of glucose in the bloodstream.
Later, when the blood glucose level begins to drop below normal, the pancreas reduces its secretion of insulin, and the "alpha cells" of the islets of Langerhans commence secretion of a hormone known as "glucagon." Glucagon stimulates the conversion of glycogen in the liver into glucose by activating another enzyme known as liver phosphorylase. This, in turn, results in release of glucose into the bloodstream for transport throughout the body.
From the foregoing, it will be appreciated that the pancreas and the liver play a major role in regulating the level of glucose in the bloodstream. Unfortunately, the delicate balance between the actions of the pancreas and the liver can be easily upset. For example, it is not uncommon for the pancreas to suffer damage so that it no longer secretes adequate levels of insulin. This condition is known as "diabetes mellitus," or more commonly, simply "diabetes." Serious cases of diabetes often exhibit a total cessation of insulin secretion.
As would be expected, insufficient secretion of insulin substantially reduces the transport of glucose into most tissues of the body. (The most notable exception is the brain; glucose transport across the blood-brain barrier is dependent upon diffusion rather than insulin-mediated transport.) Further, the glucose regulatory function is also impaired since, in the absence of insulin, little glucose is stored in the liver during times of excess and, hence, is not available for subsequent release in times of glucose need.
One result of the lack of sufficient quantities of insulin in the body is a rise in the blood glucose concentration. This causes the osmotic pressure in extracellular fluids to rise above normal, which in turn often results in significant cellular dehydration. This problem is exacerbated by the action of the kidneys which act to remove excessive quantities of glucose from the blood; the increase in glucose concentration in the kidneys causes yet additional fluids to be removed from the body. Thus, one of the significant effects of diabetes is the tendency for dehydration to develop.
However, an even more serious effect occurs because of the failure of body tissues to receive adequate levels of glucose. In the absence of adequate levels of glucose, the metabolism of body cells switches from carbohydrate metabolism to fat metabolism. When the body is required to depend heavily upon fat metabolism for its energy, the concentration of acetoacetic acid and other keto acids rises to as much as thirty times normal, thus causing a reduction in the pH of the blood below its normal pH level of 7.4.
Again, this problem is exacerbated by the kidneys. As the kidneys remove the various keto acids from the blood, substantial amounts of sodium are also lost, thereby resulting in even further decreases in blood pH. If the blood pH is reduced to below about 7.0, the diabetic person will enter a state of coma; and this condition is usually fatal.
The generally accepted treatment for diabetes is to administer enough insulin so as to restore carbohydrate metabolism. Traditionally, administration of insulin has been by injections into the peripheral circulation, either from an intramuscular or subcutaneous injection. Although widely used, this form of treatment has several disadvantages.
First, using peripheral insulin administration, only about ten percent of the administered insulin reaches the liver, as compared to approximately fifty percent in normal persons. As a consequence, hepatic glucose production is not reduced first; rather, blood glucose is lowered due to the presence of high levels of insulin in the peripheral circulation by increased utilization of the blood glucose by other tissues (such as muscle and fat). Hence, normal levels of blood sugar are achieved only by carefully matching any increased peripheral utilization of blood sugar to an increased hepatic production. This is inherently much more difficult than simply decreasing hepatic glucose production.
Additionally, these traditional administration methods fail to provide the type of control over the blood glucose concentration that occurs in a normal person. Clearly, once- or twice-daily injections of insulin cannot supply controlled variable amounts of insulin in response to changing metabolic demands during the course of the day. Hence, when using traditional insulin administration methods, the blood glucose content tends to fluctuate between normally high and low concentrations. Significantly, there are some indications that such periodic rise and fall of glucose concentrations between hyperglycemia and hypoglycemia contributes to devastating vascular and neurological complications over a period of time. (It is not uncommon, for example, for a long-term diabetic to experience atherosclerosis, arteriosclerosis, hypertension, severe coronary heat disease, retinopathy, cataracts, chronic renal disease, or loss of circulation in the extremities.)
Another consequence of massive injections of insulin on a periodic basis is that excessive amounts of insulin occasionally enter the bloodstream, thereby causing glucose to be rapidly transported into the cells and decreasing the blood glucose to substantially below normal levels. Unfortunately, diabetic patients already have little glucose reserve, since the liver, in its state of under-insulinization, is already releasing glucose. Consequently, the blood sugar level will plummet despite adequate levels of counterregulatory hormones (such as glucagon, epineephrine, norepinephrine, and growth hormones), which normally would increase liver production of glucose in emergency situations.
Importantly, if the blood glucose level is reduced too much, there will be insufficient glucose to diffuse across the blood-brain barrier, and the brain and central nervous system will begin to suffer from depressed metabolism. This hypoglycemic reaction (having a progression of symptoms from nervousness, sweating, stupor, and unconsciousness to occasionally irreparable brain damage), will occur until sugary substances are taken either by mouth or intravenously.
The resulting ongoing cycle between hyperglycemia and hypoglycemia has created a basic rift in the philosophy of diabetic control. The "tight control" philosophy claims that the long-term devastations of diabetes (that is, blindness, heart attacks, kidney failure, and loss of extremities), are due to abnormally elevated sugar levels. Those ascribing to this "tight control" philosophy strive to keep blood sugar within the normal range even at the risk of frequent (more than once a week) hypoglycemic reactions. The converse "loose control" philosophy is based upon the presumption that the basic premise of the "tight control" philosophy has yet to be proved and that the considerable risks of hypoglycemic reactions are not worth an unproved benefit.
In an effort to avoid the undesirable effects of the traditional insulin administration methods, various closed and open loop control delivery systems have been developed. Closed loop delivery systems are synonymous with prolonged hospitalization. Additionally, they are awkward to wear, they require tubing sets and implanted needles and, in spite of claims made to the contrary, they can malfunction ("surge"), usually at the most inconvenient hours.
Open loop delivery systems, on the other hand, actually produce a more sustained, if somewhat better regulated, hyperinsulinemic state. The therapists involved persist in using both open and closed loop systems to deliver insulin peripherally, thereby giving rise to many of the difficulties already mentioned.
Consequently, due to the problems and difficulties set forth above, those skilled in the art of treating diabetes have sought to find improved methods for administering therapeutic insulin to diabetic individuals. Perhaps one of the most promising insulin administration methods which is currently being investigated comprises the administration of insulin via the peritoneum.
The peritoneum is the largest serous membrane in the body and consists (in the male) of a closed sac, a part of which is applied against the abdominal parietes, while the remainder is reflected over the contained viscera. (In the female, the peritoneum is not a closed sac, since the free ends of the uterine and fallopian tubes open directly into the peritoneal cavity.)
The part of the peritoneum which lines the abdominal wall is named the parietal peritoneum and that which is reflected over the contained viscera constitutes the mesenteric (visceral) peritoneum. The space between the parietal and mesenteric layers of the peritoneum is called the peritoneal cavity. However, under normal conditions, this "cavity" is merely a potential one, since the parietal and mesenteric layers are typically in contact.
Of particular significance, a portion of the blood circulation of the peritoneum leads directly into the portal venous system. Hence, any insulin absorbed by the peritoneum would potentially have nearly direct access to the liver. As a result, such insulin would first be available to reduce hepatic glucose production, and the insulin could, therefore, potentially function more effectively in its glucose regulatory capacity.
For a number of years, it has been well-known that the peritoneal membrane will function fairly effectively as an exchange membrane for various substances. Thus, as early as 1923, peritoneal dialysis was first applied clinically. At the present time, peritoneal dialysis is being used with increasing frequency to treat individuals suffering from end-stage renal disease.
In a typical peritoneal dialysis treatment, approximately two liters of dialysate is infused into the peritoneal cavity. Then, after the dialysate has remained within the peritoneal cavity for a period of time, thereby permitting the necessary diffusion across the peritoneal membrane, the dialysate is removed. This procedure is typically repeated a number of times during each dialysis treatment. Thus, in simple terms, the peritoneal cavity, together with the dialysate, functions as an artificial kidney.
The performance of peritoneal dialysis necessarily requires some type of peritoneal access device. The first peritoneal access device was a piece of rubber tubing temporarily sutured in place. By 1960, peritoneal dialysis was becoming an established form of artificial kidney therapy; and, in order to lessen the discomfort of repeated, temporary punctures into the peritoneal cavity, various access devices permitting the painless insertion of acute or temporary peritoneal catheters were developed.
The most common peritoneal access device is of the Tenckhoff type in which a capped, percutaneous, silastic tube passes through the abdominal wall into the peritoneal cavity. Another peritoneal access device (the "Gottloib" prosthesis) consists of a short, "gold tee" shaped device which is adapted to be placed under the skin with a hollow tubular portion extending just into the peritoneal cavity. This cavity is designed specifically to allow the insertion of an acute peritoneal catheter (or trocar) through the skin and down through this access tubing directly into the peritoneal cavity.
Another device consists of a catheter buried underneath the skin and extending into the peritoneal cavity via a long tubing. Peritoneal dialysis is performed by inserting a large needle into the subcutaneous portion of the catheter.
When using such access devices, a variety of drugs or other fluids have sometimes been added to the large volumes of peritoneal dialysis solutions and thereby instialled into the peritoneal cavity for various therapeutic reasons. Some examples of these drugs are antibiotics, amino acids, and insulin. However, such therapeutic maneuvers are merely fortuitous, in that the clinician is simply taking advantage of a particular situation, that is, a peritoneal access device implanted in a particular group of patients. Importantly, there are cogent reasons for not using existing, permanent peritoneal access devices for simple drug injections in a wide variety of patients not suffering from end-stage renal disease.
First, the majority of prior art peritoneal access devices are long, clumsy, percutaneous, infection-prone silastic tubes. Hence, it is undesirable that any patient would wear such a device on a permanent or semi-permanent basis, unless it is absolutely necessary.
In addition, most of the prior art peritoneal access devices have a relatively large internal volume, that is, relatively large volumes of fluid are required in order to fill the devices. As mentioned above, during a typical dialysis treatment, approximately two liters of dialyzing fluid is injected into the peritoneal cavity at one time. Thus, when existing devices are used for purposes of peritoneal dialysis, the relatively large internal volume of the device is of little consequence. However, when injecting small quantities of fluid or drugs into the peritoneal cavity, this volume is a very real hindrance since the injected fluid may simply remain within the device itself instead of entering the peritoneal cavity.
Further, it has been found that bacteria will sometimes accumulate and grow within the prior art access devices. Also, the prior art peritoneal access devices often become obstructed by body cells and/or bacterial after they are implanted in a patient. In many cases, such obstruction cannot be eliminated without damaging the device, and the access device must, therefore, be removed.
Accordingly, it would be an improvement in the art to provide a peritoneal catheter apparatus which can be used to inject small volumes of fluid into the peritoneal cavity and which would minimize the opportunity for catheter obstruction. It would also be an improvement in the art to provide a peritoneal injection catheter apparatus and method which minimizes the accumulation or growth of body cells on the catheter. In addition, it would be an improvement in the art to provide an apparatus and method for minimizing the occurrence of bacterial growth on or in a peritoneal injection catheter. Further, it would be an improvement in the art to provide an apparatus and method for minimizing the occurrence of peritoneal injection catheter obstruction which would preserve the structural integrity of the catheter. Such devices and methods are disclosed and claimed herein.